Cellular metabolomics of pulmonary fibrosis, from amino acids to lipids

Roque, Willy; Romero, Freddy

doi:10.1152/ajpcell.00586.2020

Cited by 44 publications

(25 citation statements)

References 46 publications

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“…Because of the remarkable metabolic and regulatory functions of amino acids, the levels of amino acids in the bodies of people with various diseases are usually different from those in healthy individuals. There have been many reports of alterations in plasma amino acid concentrations in diseases, such as liver fibrosis, non-small cell lung cancer, aortic dissection, first-episode psychosis, and type-2 diabetes mellitus (Hameed et al 2020;Li et al 2019;Roque and Romero 2021;Zhou et al 2020).…”

Section: Discussionmentioning

confidence: 99%

“…As a result, amino acids have become a growing area of interest in the field of metabonomics, which aims to characterize the metabolic responses of biological systems to external or internal disturbances. Existing research on the association between amino acid metabolic profiles and progression of diseases including cancer, diabetes, arthritis, heart disease, and Alzheimer's disease (Hameed et al 2020;Li et al 2019;Roque and Romero 2021;Zhou et al 2020), suggests that targeting amino acids using metabolomics approaches could lead to major discoveries in objective disease diagnosis, target drug discovery, bioscience, etc. However, scarcely any studies have focused on changes in the amino acid metabolite profiles of patients with MMD.…”

Section: Introductionmentioning

confidence: 99%

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Targeted metabolomics analysis of serum amino acid profiles in patients with Moyamoya disease

Liu¹,

Jin

Wang

et al. 2021

Amino Acids

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Amino acids are one of the main metabolites in the body, and provide energy for the body and brain. The purpose of this study is to provide a profile of amino acid changes in the serum of patients with Moyamoya disease (MMD) and identify potential disease biomarkers. In this paper, we quantitatively determined the serum amino acid metabolic profiles of 43 MMD patients and 42 healthy controls (HCs). T test, multivariate statistical analysis, and receiver operating characteristic (ROC) curve analysis were used to identify candidate markers. Thirty-nine amino acids were quantified, and 12 amino acid levels differed significantly between the MMD patients and HCs. Moreover, based on ROC curve analysis, four amino acid (l-methionine, l-glutamic acid, β-alanine and o-phosphoserine) biomarkers showed high sensitivity and specificity (AUC > 0.90), and showed the best sensitivity and specificity in MetaboAnalyst 5.0 using binary logistic regression analysis. We have provided serum amino acid metabolic profiles of MMD patients, and identified four potential biomarkers which may both provide clinicians with an objective diagnostic method for early detection of MMD and further our understanding of MMD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeted metabolomics analysis of serum amino acid profiles in patients with Moyamoya disease

Liu¹,

Jin

Wang

et al. 2021

Amino Acids

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“…They can initiate cell signaling cascades, regulate various biological procedures [ 3 ], and provide direct information of the state of cells [ 4 ]. Metabolomics data sets link cell activities with metabolic pathways as well as biological information in patients and healthy groups [ 5 , 6 ]. Therefore, the detection of metabolites shows significant potentials in the fundamental studies and clinical applications to investigate physiological activities [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Human metabolite detection by surface-enhanced Raman spectroscopy

Liu

2022

Materials Today Bio

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Metabolites are important biomarkers in human body fluids, conveying direct information of cellular activities and physical conditions. Metabolite detection has long been a research hotspot in the field of biology and medicine. Surface-enhanced Raman spectroscopy (SERS), based on the molecular “fingerprint” of Raman spectrum and the enormous signal enhancement (down to a single-molecule level) by plasmonic nanomaterials, has proven to be a novel and powerful tool for metabolite detection. SERS provides favorable properties such as ultra-sensitive, label-free, rapid, specific, and non-destructive detection processes. In this review, we summarized the progress in recent 10 years on SERS-based sensing of endogenous metabolites at the cellular level, in tissues, and in biofluids, as well as drug metabolites in biofluids. We made detailed discussions on the challenges and optimization methods of SERS technique in metabolite detection. The combination of SERS with modern biomedical technology were also anticipated.

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“…Recently the involvement of aberrant metabolic and lipid pathways have been implicated to affect IPF pathophysiology. Altered metabolism of the amino acids glycine, glutamine and arginine and dysregulated glycolysis was shown to promote profibrotic phenotypes via TGF-ß dependent pathways ( Zhao et al, 2017 ; Gaugg et al, 2019 ; Roque and Romero, 2021 ). For lipids, increased levels of long-chain and medium chain fatty acids have been reported in IPF lungs and macrophage reprogramming with increased fatty acid beta oxidation have been described.…”

Section: Introductionmentioning

confidence: 99%

Changes in serum metabolomics in idiopathic pulmonary fibrosis and effect of approved antifibrotic medication

et al. 2022

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Idiopathic pulmonary fibrosis (IPF) is a progressive disease with significant mortality and morbidity. Approval of antifibrotic therapy has ameliorated disease progression, but therapy response is heterogeneous and to date, adequate biomarkers predicting therapy response are lacking. In recent years metabolomic technology has improved and is broadly applied in cancer research thus enabling its use in other fields. Recently both aberrant metabolic and lipidomic pathways have been described to influence profibrotic responses. We thus aimed to characterize the metabolomic and lipidomic changes between IPF and healthy volunteers (HV) and analyze metabolomic changes following treatment with nintedanib and pirfenidone. We collected serial serum samples from two IPF cohorts from Germany (n = 122) and Spain (n = 21) and additionally age-matched healthy volunteers (n = 16). Metabolomic analysis of 630 metabolites covering 14 small molecule and 12 different lipid classes was carried out using flow injection analysis tandem mass spectrometry for lipids and liquid chromatography tandem mass spectrometry for small molecules. Levels were correlated with survival and disease severity. We identified 109 deregulated analytes in IPF compared to HV in cohort 1 and 112 deregulated analytes in cohort 2. Metabolites which were up-regulated in both cohorts were mainly triglycerides while the main class of down-regulated metabolites were phosphatidylcholines. Only a minority of de-regulated analytes were small molecules. Triglyceride subclasses were inversely correlated with baseline disease severity (GAP-score) and a clinical compound endpoint of lung function decline or death. No changes in the metabolic profiles were observed following treatment with pirfenidone. Nintedanib treatment induced up-regulation of triglycerides and phosphatidylcholines. Patients in whom an increase in these metabolites was observed showed a trend towards better survival using the 2-years composite endpoint (HR 2.46, p = 0.06). In conclusion, we report major changes in metabolites in two independent cohorts testing a large number of patients. Specific lipidic metabolite signatures may serve as biomarkers for disease progression or favorable treatment response to nintedanib.

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Cellular metabolomics of pulmonary fibrosis, from amino acids to lipids

Cited by 44 publications

References 46 publications

Targeted metabolomics analysis of serum amino acid profiles in patients with Moyamoya disease

Targeted metabolomics analysis of serum amino acid profiles in patients with Moyamoya disease

Human metabolite detection by surface-enhanced Raman spectroscopy

Changes in serum metabolomics in idiopathic pulmonary fibrosis and effect of approved antifibrotic medication

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